The implantation effect refers to a transient reduction in seizure frequency following intracranial electrode insertion in patients with epilepsy, independent of therapeutic intervention. This retrospective study examined potential clinical and demographic predictors of the implantation effect in 51 patients who underwent stereoelectroencephalographic investigation between December 2018 and February 2020. Follow-up data were collected at 1, 3, 6, and 12 months postimplantation. A ≥50% reduction in seizure frequency defined responder status. Responder rates were 71.4% at 1 month, 35.0% at 3 months, 33.3% at 6 months, and 50.0% at 12 months. Complete seizure freedom was observed in 42.9% of patients at 1 month and 20.0% at 3 months. No significant associations were found between seizure reduction and age, sex, imaging findings, cortical stimulation, electrode count, or preimplantation antiseizure medication type or load. The lack of predictive variables, alongside seizure reduction in patients with previously uncontrolled epilepsy, supports the hypothesis that electrode-induced microlesions may transiently disrupt epileptogenic networks. The quantity of electrodes did not influence outcomes, suggesting that implantation location may be more important. The effects of antiseizure medications remain unclear due to limited tracking of dosage or regimen changes. Further prospective research is needed to clarify the mechanisms underlying the implantation effect.

Constrictor stimuli set arterial tone through coupling processes dependent (electromechanical) and independent (pharmacomechanical) of VM. As the latter receives limited attention, we conducted a focused examination of the cerebral circulation to identify key signalling kinases involved in tone development and their role in regulating blood flow. A multiscale approach was implemented extending from cells to live brain and including myography, western blotting, immunolabelling, two-photon microscopy and modelling. We began by superfusing a G protein-coupled receptor agonist (U46619) onto isolated mouse cerebral arteries to drive a concentration-dependent constriction. Using pharmacology to separate the two processes, electromechanical coupling notably preceded pharmacomechanical, the latter tied to protein kinase C (PKC) activation. PKCδ mediated the pharmacomechanical response, irrespective of whether the agonist was superfused or discretely applied to elicit focal non-electrical constriction. Further analysis revealed (1) the translocation of PKCδ to the membrane, indicating its activation, and (2) the identification of C-kinase-activated protein phosphatase-1 inhibitor of 17 kDa (CPI-17) and heat shock protein 27 (HSP27) as downstream phosphorylation targets of PKCδ involved in regulating tone. Focal non-electrical constriction was observed in vivo along penetrating arterioles, responses dependent on PKCδ. Key findings were confirmed in human cerebral arteries, and modelling demonstrated how focal, non-electrical control sets cerebral blood flow distribution. We conclude pharmacomechanical coupling is robust in cerebral arteries and enabled by PKCδ through phosphorylation of CPI-17 and HSP27. This process allows arteries to focally constrict and presumptively optimize blood flow distribution when discrete stimuli are produced. We discuss how aberrant pharmacomechanical control could underlie focal vascular pathobiology and if PKCδ could be a target for therapeutic control. KEY POINTS: Constrictors set arterial tone through coupling processes dependent (electromechanical) and independent (pharmacomechanical) of membrane potential. The relative contribution of electro- and pharmacomechanical coupling to cerebral arterial tone depends to the concentration and area to which constrictors are applied. Protein kinase Cδ is a key transduction protein within pharmacomechanical coupling that enables a focal segment of cerebral artery to constrict independently of the lengthier vessel. Focal constriction is observed in live cerebral microcirculation and it helps set proper blood flow distribution within the brain.

Invasive extra-operative monitoring for drug-resistant epilepsy is primarily conducted using stereo-electroencephalography (SEEG) and subdural grids (SDG). This study aims to provide a comprehensive comparison of the two methods. This systematic review was conducted in accordance with PRISMA guidelines. A comprehensive literature search was performed using PubMed, Scopus, Web of Science, and the Cochrane Database. The primary outcomes assessed included postoperative seizure outcome, complications, neurological deficits, and pain. All original English-language studies published up until January 2025 were reviewed, and the risk of bias was evaluated using the Newcastle-Ottawa Scale. Seven studies involving a total of 1,156 patients who underwent SEEG and 737 patients who underwent SDG were included. The pooled analysis demonstrated higher odds of seizure freedom in the SEEG group compared with the SDG group (OR = 1.72, 95

Abstract The myogenic response is the key autoregulatory mechanism setting cerebral blood flow and its mechanistic foundation is intimately tied to depolarization and the voltage gating of L-type Ca 2+ channels (Ca V 1.2). While critical, this study argues for an additional mechanism, that of pressure itself enhancing Ca V 1.2 activity via cooperative gating and perimembrane trafficking of channel’s subunits. These novel insights were pursued at the cell level using patch-clamp electrophysiology and advanced microscopy, and then functionally in pressurized arteries through measures of tone and intracellular [Ca 2+ ] i . Key findings were confirmed in mutant mice with disrupted functional coupling and translated into arteries procured from human brain tissue. From cerebral blood flow simulations of semi-realistic microvascular networks, we predict that loss of this alternative mechanism leads to maldistribution of brain blood flow and potentially a diminishment of cognitive function. This study reveals previously unrecognized pressure-sensitive Ca V 1.2 regulatory mechanism that advances understanding of cerebral blood flow. Significance Blood pressure sets base arterial constriction - a response critical for blood flow control in brain. This response is tied to Ca V 1.2 channels and their presumptive and exclusive activation by voltage, reasoning now under great scrutiny. We establish herein with advance methods, a second mode of Ca V 1.2 pressure regulation, that of enhanced functional cooperativity among neighboring channels. This novel mechano-response is tied to PKCα and its ability to set channel phosphorylation and Ca V 1.2 trafficking. Ca V 1.2 pressure regulation was observed in human tissues and its disruption (mutant mice) impaired myogenic tone in the presence of preserved voltage control. Cerebral microvascular modeling highlights that losing this mechanism destabilizes blood flow distribution in brain, the knock-on effect being comprised cognitive function.

More than 15 million patients worldwide suffer from drug-resistant epilepsy (DRE). Surgical removal of the seizure onset zone (SOZ)-the brain region(s) from where seizures arise-is the best available treatment for these patients, with post-surgical outcomes depending on the successful identification and resection of the SOZ. Most commonly, SOZ mapping localizes ictal activity occurring spontaneously or evoked by cortical stimulation (CS) during pre-surgical evaluation of patients with epilepsy using stereoelectroencephalography (SEEG). Mapping events such as interictal epileptiform discharges (IEDs), paroxysmal hypersynchronic electrical discharges that often occur outside ictal discharges or during CS, have been less used for SOZ localization. We test the hypothesis that IEDs triggered by CS via SEEG investigation can contribute to the mapping of the SOZ. We evaluated the impact of CS on IEDs in patients investigated with SEEG on epilepsy surgery. We recorded intracranial signals from 30 DRE patients (seizure-free post-surgery). Bipolar and high-frequency (50 Hz) CS were performed with a pulse width of 300 µs and current spanning of 1-8 mA. IEDs were automatically detected pre- and post-stimulation, and their normalized absolute changes were quantified within and outside the SOZ (identified by ictal discharges). We found that the IED rates significantly increased post-stimulation compared with pre-stimulation within the SOZ, while no significant change was observed outside the SOZ (linear mixed-effect model, P-value < 0.001, and AUC = 98% for SOZ and 71% for non-SOZ). This effect was present regardless of whether the stimulation was applied to the SOZ or non-SOZ regions, indicating a broader effect of stimulation on the SOZ. Our results offer a quantitative tool for identifying epileptogenic areas in patients with DRE, enhancing the mapping and localization of the SOZ and potentially improving surgical outcomes.

OBJECTIVE:The aim of this study was to retrospectively compare robot-assisted and manual frame-based stereoelectroencephalography (SEEG) with respect to timing, complications, and outcomes in a high-volume epilepsy surgery center. METHODS:All patients with drug-resistant epilepsy who underwent SEEG from 2000 to 2020 were collected for a retrospective-and from 2017 onward, prospective-database. RESULTS:A total of 192 SEEG procedures consisted of 88 robot-assisted and 104 manual frame-based cases. Both groups were of similar age, gender distribution, and duration of epilepsy. A mean of 10.9 electrodes were implanted for the robot-assisted group versus 9.3 electrodes in the manual frame-based group (p < 0.01) with a mean implantation time per electrode of 8.2 ± 3.4 versus 16.1 ± 7.7 minutes, respectively (p < 0.01). Complications were low in both groups; intracranial hemorrhage was observed in 6.8% and 5.8%, respectively. CONCLUSIONS:Using a stereotactic robot for SEEG electrode insertion can significantly decrease operative time.

OBJECTIVE:This study was undertaken to determine whether bilateral independent or unclear (BI/U) scalp electroencephalographic (EEG) ictal onset patterns may predict the diagnostic yield of stereo-electroencephalography (SEEG) and inform surgical decision-making in patients with focal drug-resistant epilepsy. METHODS:We conducted a retrospective cohort study of consecutive patients with focal drug-resistant epilepsy and BI/U ictal onset on scalp EEG who underwent SEEG evaluation at our center between January 2012 and December 2024. All patients had undergone noninvasive and invasive presurgical assessments. Surgical outcomes were determined using the Engel classification following at least 1 year of postoperative follow-up. A blinded decision validation substudy was also performed, where the team made decisions regarding SEEG and surgical interventions when patients found to have a single SEEG seizure onset zone (SOZ) were presented. Responses were stratified to inform the added diagnostic value of SEEG. RESULTS:Of 255 SEEG cases screened, 84 patients (33%) had BI/U ictal onset on scalp EEG. The cohort was 56% female, with a median seizure onset age of 12 years (interquartile range = 6-20); 65.5% had temporal lobe epilepsy (TLE). A single SOZ was identified in 14.3% of cases (TLE: 14.5%, extratemporal: 13.8%). These patients had shorter SEEG recording durations (mean = 11 vs. 15.79 days in those with multifocal SEEG SOZs, p = .009). Curative focal resections were performed in 12% (n = 10), with long-term Engel I outcomes achieved in one patient of the entire cohort (1.2%). Palliative resections occurred in 26% (n = 22), with Engel I outcomes in 7% (n = 6). In 50% of the blinded cases, the epilepsy surgery team reported that they would not have recommended SEEG based on phase I data. SIGNIFICANCE:In patients with BI/U ictal onset on scalp EEG, the likelihood of identifying a single SEEG SOZ, and subsequently achieving seizure freedom, is low. Scalp EEG ictal onset patterns may aid in triaging candidates for invasive evaluation, informing patients regarding presumed SEEG outcome, and avoiding unnecessary surgical procedures.

Scalp electroencephalography (EEG) may reveal bilateral independent or unclear (BI/U) ictal onset patterns in patients with focal drugresistant epilepsy, presenting a challenge to surgical decision making. The utility of stereoelectroencephalography (SEEG) in this subgroup, particularly the probability of delineating a single seizure onset zone (SOZ) that would permit curative resection, remains poorly understood. This study examined whether BI/U scalp EEG findings could predict SEEG outcomes in this population. We conducted a retrospective cohort study of consecutive patients with focal drugresistant epilepsy and BI/U ictal onset on scalp EEG who underwent SEEG evaluation at the London Health Sciences Centre (Ontario, Canada) between January 2012 and December 2024. All patients had undergone noninvasive and invasive presurgical assessments. Surgical outcomes were determined using the Engel classification following at least one year of postoperative followup. A blinded decision validation substudy was also performed. Blinded to actual outcomes, the team made decisions regarding SEEG and surgical interventions when patients found to have a single SEEG SOZ were presented. Responses were stratified to inform the added diagnostic value of SEEG. Of 255 SEEG cases screened, 84 patients (33%) met inclusion criteria. The cohort was 56% female, with a median seizure onset age of 12 years (IQR 6[ndash]20); 65.5% had temporal lobe epilepsy (TLE). A single SOZ was identified in 14.3% of cases (TLE: 14.5%, extratemporal: 13.8%). Patients with a single SEEG SOZ were found to have shorter recording durations (mean of 11 vs 15.79 days in those with multifocal SEEG SOZs; p=0.009). Curative focal resections were performed in 12% (n=10), with longterm Engel I outcomes achieved in one patient (1.2%). Palliative resections occurred in 26% (n=22), with Engel I outcomes in 7% (n=6). In 50% of the blinded cases, the epilepsy surgery team reported that they would not have recommended SEEG based on phase I data. These findings suggest that patients with BI/U scalp EEG SOZs may be associated with a low likelihood of identifying a single SEEG SOZ and curative outcome. Using BI/U scalp EEG ictal onset as a predictor in preoperative decisionmaking will assist in refining SEEG candidate selection in this large subgroup. ### Competing Interest Statement J. G. B holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. G.P. receives Xenon X TOLE2/3 and X ACKT clinical trials and Elsevier Neuroimage Editorial Honoraria. Revenues from the above activities are allocated to a research account. GP is also funded by AMOSO (Academic Medical Organization of Southwestern Ontario) Opportunities Fund, Western Strategic Support for CIHR Success Seed program, NSERC Discovery Grant, NSERC RTI Grant, Western CNS Internal Competition Grant, Lawson Internal Research Grant Fund, CNS Department Starting Grant. All other authors confirm no competing interests for this research. ### Funding Statement No funding was received towards this work specifically. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Western University Health Science Research Ethics Board (127171 108606) in London, Ontario, Canada gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

OBJECTIVE:Despite the general safety and efficacy of epilepsy surgery, there is evidence that epilepsy surgery remains underutilized. Although there are an increasing number of studies reporting epilepsy surgery in older adults, there is no consensus on whether epilepsy surgery is efficacious or safe for this population. Our objective was to systematically assess the efficacy as well as safety of resective surgery in people aged 50 years or older with drug-resistant epilepsy.METHODS:We considered studies that examine the efficacy and safety of epilepsy surgery in adults aged 50 years and older. Study eligibility was limited to studies carried out after 1990, with a minimum of 10 participants and 6 months of follow-up. We searched the following databases for published studies: Ovid MEDLINE, Ovid Embase, Cumulative Index to Nursing and Allied Health Literature, PsychInfo, and Web of Science Conference Proceedings Citation Index - Science. The risk of bias of each included study was independently assessed by two reviewers using the MINORS (Methodological Index for Non-Randomized Studies) instrument.RESULTS:Eleven case series and 14 cohort studies met the criteria for inclusion, for a total of 1111 older adults who underwent epilepsy surgery along with 4111 adults younger than 50 years as control groups. The pooled cumulative incidence of older adults achieving seizure freedom after resective surgery was 70.1% (95% confidence interval [CI] = 65.3-74.7). There was no evident difference in the incidence of seizure freedom among older adults as compared to younger adults (risk ratio [RR] = 1.05, 95% CI = .97-1.14) in cohort studies. The pooled cumulative incidence of perioperative complications in older adults was 26.2% (95% CI = 21.3-31.7). Among them, 7.5% (95% CI = 5.8-9.5) experienced major complications. Older adults were significantly more at risk of experiencing any complication than younger adults (RR = 2.8, 95% CI = 1.5-5.4).SIGNIFICANCE:Despite important considerations, epilepsy surgery may be considered appropriate among carefully selected individuals older than 50 years.

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a treatment option for focal drug-resistant epilepsy. In previous studies, this technique has shown seizure reduction by ≥50% in 50% of patients at 1 year. However, the relationship between the location of the ablation within the epileptogenic network and clinical outcomes remains poorly understood. Seizure outcomes were analyzed for patients who underwent SEEG-guided RF-TC and across subgroups depending on the location of the ablation within the epileptogenic network, defined as SEEG sites involved in seizure generation and spread. Eighteen patients who had SEEG-guided RF-TC were included. SEEG-guided seizure-onset zone ablation (SEEG-guided SOZA) was performed in 12 patients, and SEEG-guided partial seizure-onset zone ablation (SEEG-guided P-SOZA) in 6 patients. The early spread was ablated in three SEEG-guided SOZA patients. Five patients had ablation of a lesion. The seizure freedom rate in the cohort ranged between 22% and 50%, and the responder rate between 67% and 85%. SEEG-guided SOZA demonstrated superior results for both outcomes compared to SEEG-guided P-SOZA at 6 months (seizure freedom p = .294, responder rate p = .014). Adding the early spread ablation to SEEG-guided SOZA did not increase seizure freedom rates but exhibited comparable effectiveness regarding responder rates, indicating a potential network disruption.

OBJECTIVE:To investigate the effects of vagus nerve stimulation (VNS) on the seizure frequency in patients with drug-resistant epilepsy (DRE) and bilateral temporal lobe epilepsy (bi-TLE). Additionally, we aimed to determine the safety of VNS and its side effects. METHODS:Our retrospective study included 17 patients with bi-TLE who underwent VNS-device implantation at our center from 1997 to 2019. The main outcome was a reduction in seizure frequency. Bitemporal cases were confirmed using scalp electroencephalography (EEG) or invasive electroencephalography (iEEG). RESULTS:The median age at seizure onset was 18 years. Bi-TLE was confirmed by scalp EEG in 47 % and by iEEG in 53 % of the patients. The median follow-up period was 36 months. The median seizure frequency per month before and after VNS was 9.5 (IQR = 4.3-35.3) and 2 (IQR = 0.8-4.2), respectively. Compared to baseline, 70.5 % of the patients achieved ≥ 50 % reduction in seizure frequency, whereas 35.3 % experienced either no or minimal reduction in seizure frequency. The response rate (>50 % reduction in seizure frequency) was 87.5 % in patients who underwent scalp EEG and 55.5 % in those who underwent iEEG. For VNS treatment, the median follow-up was at 36 months (IQR = 17-46.5). Adverse effects were observed in 59 % of the patients, including cough and hoarseness. DISCUSSION:Therapeutic choices are limited in cases of drug-resistant bi-TLE. Our study on VNS-device implantation in bi-TLE suggests a positive outcome.

A large proportion of those affected by epilepsy live in resource-poor areas. The Epilepsy surgery in low-resource settings Task Force from the ILAE undertook a survey in Africa and Latin America to identify fellowships in Epilepsy and EEG as well as in Epilepsy Surgery. The results revealed a significant shortage of training programs in these two regions of the globe.

PURPOSE:Drug-resistant epilepsy (DRE) affects one-third of patients with focal epilepsy. A large portion of patients are not candidates for epilepsy surgery, thus alternative options, such as vagus nerve stimulation (VNS), are proposed. Our objective is to study the effect of vagus nerve stimulation on lesional versus non-lesional epilepsies. METHODS:This is a retrospective cohort study in a single center in London, Ontario, which includes patients with DRE implanted with VNS, implanted between 1997-2018 and the date of analysis is December 2023. PARTICIPANTS:Patients implanted with VNS were classified by lesional (VNS-L) and non-lesional (VNS-NL) based on their MRI head findings. We further subdivided the VNS groups into patients with VNS alone versus those who also had additional epilepsy surgeries. RESULTS:A total of 29 patients were enrolled in the VNS-L, compared to 29 in the VNS-NL. The median age of the patients in the study was 31.8 years, 29.31 % were men (N = 17). 41.4 % (n = 12) of the patients were VNS responders (≥50 % seizure reduction) in the VNS-L group compared to 62.0 % (n = 18) in the VNS-NL group (p = 0.03). When other epilepsy surgeries were combined with VNS in the VNS-L group, the median rate of seizure reduction was greater (72.4 (IQR 97.17-45.88) than the VNS-NL group 53.9 (IQR 92.22-27.92); p = 0.27). CONCLUSIONS:VNS is a therapeutic option for patients with lesional epilepsy, with slightly inferior results compared to patients with non-lesional epilepsy. Patients implanted with VNS showed higher seizure reduction rates if they had previous epilepsy surgeries. This study demonstrates that VNS in lesional epilepsies can be an effective treatment.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Objective: To analyze the involvement of the posterior cingulate gyrus (PCG) during mesial temporal lobe seizures (MTLS).Methods: We retrospectively reviewed the stereo-EEG (SEEG) recordings of patients with MTLS performed in our institution from February 2013 to December 2020. Only patients who had electrode implantation in the PCG were included. Patients with lesions that could potentially alter the seizure spread pathways were excluded. We assessed the propagation patterns of MTLS with respect to the different structures sampled.Results: Nine of 97 patients who had at least one seizure originating in the mesial temporal region met the inclusion criteria. A total of 174 seizures were analyzed. The PCG was the first site of propagation in most of the cases (8/9 patients and 77.5% of seizures, and 7/8 patients and 65.6% of seizures after excluding an outlier patient). The fastest propagation times were towards the contralateral mesial temporal region and ipsilateral PCG. Seven patients underwent standard anterior temporal lobectomy and, of these, all but one were Engel 1 at last follow up.Conclusion: We found the PCG to be the first propagation site of MTLS in this group of patients. These results outline the relevance of the PCG in SEEG planning strategies. Further investigations are needed to corroborate whether fast propagation to the PCG predicts a good surgical outcome.

Background: The incidence of drug resistant epilepsy (DRE) is around 30% patients with epilepsy. Vagus nerve stimulation (VNS) is offered to patients who are not candidates for epilepsy resective surgery, however the results of lesional cases has not been explored previously Methods: The study was a retrospective cohort study that involved patients with DRE implanted with VNS at the Epilepsy program at Western University, Ontario. We classified our VNS cohort based on brain imaging of lesional (L) and nonlesional (NL) epilepsy. Results: The median age was 31.8 years, 70.69% were females. The VNS-L group average age was 31.8 years and the NL 35.2 years. The most common abnormality was nodular heterotropias 31.34% (n=9). 16 patients underwent palliative procedures before the VNS implantation, 12 in VNS-L and 4 in VNS-NL. The median period of follow-up was 69.97 months. 62% of the VNS-L group had a seizure reduction of 50% or greater, compared to 41.38% in the VNS-NL group. Seizure freedom was 10.34% in VNS-L, compared to 6.99% in VNS-NL. Conclusions: This is the first study reporting the outcome of VNS in lesional cases. Our results suggest that VNS in lesional cases is effective. However, a large multicenteric study is needed.